Autor: |
Stumm, Jürgen, Vallecillo-García, Pedro, Vom Hofe-Schneider, Sophie, Ollitrault, David, Schrewe, Heinrich, Economides, Aris N., Marazzi, Giovanna, Sassoon, David A., Stricker, Sigmar |
Zdroj: |
Stem Cell Research; Oct2018, Vol. 32, p8-16, 9p |
Abstrakt: |
Abstract Fibro-adipogenic progenitors (FAPs) are resident mesenchymal progenitors in adult skeletal muscle that support muscle repair, but also give rise to fibrous and adipose infiltration in response to disease and chronic injury. FAPs are identified using cell surface markers that do not distinguish between quiescent FAPs and FAPs actively engaged in the regenerative process. We have shown previously that FAPs are derived from cells that express the transcription factor Osr1 during development. Here we show that adult FAPs express Osr1 at low levels and frequency, however upon acute injury FAPs reactivate Osr1 expression in the injured tissue. Osr1+ FAPs are enriched in proliferating and apoptotic cells demonstrating that Osr1 identifies activated FAPs. In vivo genetic lineage tracing shows that Osr1+ activated FAPs return to the resident FAP pool after regeneration as well as contribute to adipocytes after glycerol-induced fatty degeneration. In conclusion, reporter LacZ or eGFP-CreERt2 expression from the endogenous Osr1 locus serves as marker for FACS isolation and tamoxifen-induced manipulation of activated FAPs. Highlights • Odd skipped related 1 (Osr1) marks adult FAPs activated by acute injury • Osr1 is expressed in FAPs during phases of active myogenesis • Osr1 can be used to mark, access and lineage-trace adult injury-activated FAPs [ABSTRACT FROM AUTHOR] |
Databáze: |
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